Biology subjects

Brouze, M.

Publications and source records attributed to Brouze, M..

2 recordsLinked to original sources

bioRxiv2023

Polyadenylation of mRNAs encoding secreted proteins by TENT5 family of enzymes is essential for gametogenesis in mice.

Cytoplasmic polyadenylation plays a vital role in gametogenesis, however, the participating enzymes and substrates in mammals remain unclear. Using knockout and knock-in mouse models, we describe the essential role of 4 TENT5 poly(A) polymerases in mice fertility and gametogenesis. TENT5B and TENT5C play crucial, but redundant roles in oogenesis, with double knockout of both genes leading to oocyte degeneration. Additionally, TENT5B-GFP knock-in females display gain-of-function infertility effect with multiple chromosomal aberrations in ovulated oocytes. TENT5C and TENT5D both regulate different stages of spermatogenesis, shown by sterility of males with either genes knockout mutation. Finally, Tent5a knockout significantly lowers fertility, although the underlying mechanism is not directly related to gametogenesis. Through Direct RNA sequencing we discovered that TENT5s polyadenylate mRNAs encoding endoplasmic reticulum-targeted proteins essential for gametogenesis. Sequence motives analysis and reporter mRNA assay revealed that the presence of endoplasmic reticulum-leader represents the primary determinant of TENT5-mediated regulation.

developmental biology↗

bioRxiv2022

DIS3L, cytoplasmic exosome catalytic subunit, is essential for development but not cell viability in mice.

Among numerous enzymes involved in RNA decay, processive exoribonucleases are the most prominent group responsible for the degradation of the entire RNA molecules. The role of mammalian cytoplasmic 3-5 exonuclease DIS3L at the organismal level remained unknown. Herein we established knock-in and knock-out mouse models to study DIS3L functions in mice. DIS3L is indeed a subunit of the cytoplasmic exosome complex, which disruption leads to severe embryo degeneration and death in mice soon after implantation. These changes could not be prevented by supplementing extraembryonic tissue with functional DIS3L through the construction of chimeric embryos. Preimplantation Dis3l-/- embryos were unaffected in their morphology and ability to produce functional embryonic stem cells showing that DIS3L is not essential for cell viability. There were also no major changes in the transcriptome level for both embryonic stem cells and blastocysts, as revealed by RNA sequencing experiments. Notably, however, DIS3L knock-out led to inhibition of the global protein synthesis. These results point to the essential role of DIS3L in mRNA quality control pathways crucial for proper protein synthesis during embryo development.

molecular biology↗